sBCMA Plasma Level Dynamics and Anti-BCMA CAR-T-Cell Treatment in Relapsed Multiple Myeloma.

BACKGROUND Novel chimeric antigen receptor T-cells (CAR-T) target the B-cell maturation antigen (BCMA) expressed on multiple myeloma cells. Assays monitoring CAR-T cell expansion and treatment response are being implemented in clinical routine. METHODS Plasma levels of soluble BCMA (sBCMA) and anti-BCMA CAR-T cell copy numbers were monitored in the blood, following CAR-T cell infusion in patients with relapsed multiple myeloma. sBCMA peptide concentration was determined in the plasma, applying a human BCMA/TNFRS17 ELISA. ddPCR was performed using probes targeting the intracellular signaling domains 4-1BB und CD3zeta of the anti-BCMA CAR-T construct. RESULTS We report responses in the first five patients who received anti-BCMA CAR- T cell therapy at our center. Four patients achieved a complete remission (CR) in the bone marrow one month after CAR-T infusion, with three patients achieving stringent CR, determined by flow cytometry techniques. Anti-BCMA CAR-T cells were detectable in the peripheral blood for up to 300 days, with copy numbers peaking 7 to 14 days post-infusion. sBCMA plasma levels started declining one to ten days post infusion, reaching minimal levels 30 to 60 days post infusion, before rebounding to normal levels. CONCLUSIONS Our data confirm a favorable response to treatment in four of the first five patients receiving anti-BCMA CAR-T at our hospital. Anti-BCMA CAR-T cell expansion seems to peak in the peripheral blood in a similar pattern compared to the CAR-T cell products already approved for lymphoma treatment. sBCMA plasma level may be a valid biomarker in assessing response to BCMA-targeting therapies in myeloma patients

Incidence of low central venous oxygen saturation during unplanned admissions in a multidisciplinary intensive care unit: an observational study

INTRODUCTION: It has been shown that early central venous oxygen saturation (ScvO2)-guided optimization of hemodynamics can improve outcome in septic patients. The early ScvO2 profile of other patient groups is unknown. The aim of this study was to characterize unplanned admissions in a multidisciplinary intensive care unit (ICU) with respect to ScvO2 and outcome. METHODS: Ninety-eight consecutive unplanned admissions to a multidisciplinary ICU (median age 63 [range 19 to 83] years, median Simplified Acute Physiology Score [SAPS II] 43 [range 11 to 92]) with a clinical indication for a central venous catheter were included in the study. ScvO2 was assessed at ICU arrival and six hours later but was not used to guide treatment. Length of stay in ICU (LOSICU) and in hospital (LOShospital) and 28-day mortality were recorded. RESULTS: ScvO2 was 70% +/- 12% (mean +/- standard deviation) at admission and 71% +/- 10% six hours later (p = 0.484). Overall 28-day mortality was 18%, LOSICU was 3 (1 to 28) days, and LOShospital was 19 (1 to 28) days. Patients with an ScvO2 of less than 60% at admission had higher mortality than patients with an ScvO2 of more than 60% (29% versus 17%, p < 0.05). Changes in ScvO2 during the first six hours were not predictive of LOSICU, LOShospital, or mortality. CONCLUSION: Low ScvO2 in unplanned admissions and high SAPS II are associated with increased mortality. Standard ICU treatment increased ScvO2 in patients with a low admission ScvO2, but the increase was not associated with LOSICU or LOShospital

Improved survival rates of AML patients following admission to the intensive care unit.

Induction chemotherapy in AML patients may have life-threatening side effects requiring intensive care unit (ICU) treatment. We analyzed all AML patients receiving intensive chemotherapy at a single academic center between 01/2006-12/2016. At least one ICU admission was observed in 32% (76/240) patients, and 33% of those died following ICU admission. Whereas the ICU admission proportion remained stable, mortality after ICU admission decreased from 14% (2006-2008) to 3% (2014-2016; p = .056). The number of failing organ systems inversely correlated with surviving ICU admission (p 50% even after 14 days of ICU treatment. Progression-free and overall survival were comparable between ICU surviving patients and patients never needing ICU support. In conclusion, outcome after ICU admission of AML patients has substantially improved in recent years

Adding bendamustine to melphalan before ASCT improves CR rate in myeloma vs. melphalan alone: A randomized phase-2 trial.

Definite cure remains exceptional in myeloma patients even after high-dose chemotherapy (HDCT) with melphalan (Mel) and autologous stem cell transplantation (ASCT). Thus, improving efficacy of HDCT in MM remains an unresolved issue. This randomized phase II trial compared standard 200 mg/m2 Mel HDCT to experimental HDCT with 200 mg/m2 bendamustine, given both at days -4 and -3, combined with 100 mg/m2 melphalan at days -2 and -1 (BenMel) before ASCT as first-line consolidation in myeloma patients. The primary endpoint aimed to identify at least a 15% improvement in the complete remission rate (stringent CR + CR) after HDCT with BenMel compared with Mel alone. A total of 120 MM patients were 1:1 randomized. The rate of sCR/CR after ASCT was higher in BenMel than in Mel treated patients (70.0% vs. 51.7%; p = 0.039). Three patients in the BenMel group (5.0%) had reversible acute renal insufficiency compared with none in Mel patients. Minimal residual disease negativity (<10-5) by flow cytometry was observed in 26 (45.6%) BenMel patients and 22 (37.9%) in the Mel group (p = 0.375). Our data suggest that BenMel HDCT is safe and improves the sCR/CR rate compared with standard Mel alone

Rebound Thrombocytosis after Induction Chemotherapy is a Strong Biomarker for Favorable Outcome in AML Patients

https://scholarlycommons.pacific.edu/pacifican/1478/thumbnail.jp

Real-World Outcome in the pre-CAR-T Era of Myeloma Patients Qualifying for CAR-T Cell Therapy.

Background CAR-T cell therapy is likely to be introduced starting from 2021 in patients with relapsed/refractory myeloma (r/r MM) in Europe. In order to qualify for commercial CAR-T treatment, it is assumed that r/r MM patients will have to be exposed to at least three lines of previous treatments including lenalidomide, bortezomib and anti-CD38 treatment. However, the outcome of this particular subgroup of r/r MM patients is largely unknown whereas this knowledge is crucial to estimate the possible benefit of eventual CAR-T treatment. Methods In this non-interventional, retrospective single-center study, we analyzed all subsequent r/r MM patients treated between 01/2016 (when anti-CD38 treatment was commercially introduced in Switzerland) and 04/2020 at the University Hospital of Bern. Patients were eligible for the study if they had received at least three lines of treatment including one proteasome inhibitor (PI), one immunomodulatory drug (IMID) and one anti-CD38 antibody, and if they were in need of subsequent treatment and effectively received further lines of treatment. Results Among 56 patients fulfilling the criteria of at least three lines of treatment including PI, IMID and anti-CD38 treatment, only 34 (60%) effectively received subsequent further therapy. This suggests that 40% of r/r MM patients never receive additional treatment after at least three lines of treatment including PI, IMID and anti-CD38 treatment. For patients receiving further treatment, the median number of previous lines of treatment was 4.5 (range 2-12), including autologous stem cell transplantation in 31 (91%) patients. 13 (37%) patients were penta-refractory. The most frequently used treatment options were IMID/dexamethasone treatment in 11 (32%) patients, followed by PI/dexamethasone in 10 (29%) patients. 21 (62%) patients received two or more additional lines of therapy. The median PFS was 6.6 months (range 0-36.6 months), the median TTNT was 7.5 months (range 1.4-24.5 months) and the median OS was 13.5 months, (range 0.1-38 months) for the first subsequent treatment. The overall response rate (ORR) to the first subsequent treatment was 41%, with a median duration of the response of 5 months (range 1-37 months). 12% of the patients achieved VGPR or better, with a median duration of response of 8 months (range 3-37 months). Conclusions Myeloma patients refractory after at least three lines of anti-CD38/PI/IMID treatment have a poor prognosis with a PFS of 6.6 months and OS of 13.5 months. These data may serve as reference to compare the potential benefit of CAR-T treatment in this group of myeloma patients when available in the near future

CAR-T-Zelltherapie – eine neue Behandlungsoption

Die Mehrzahl der Rückfälle beim diffusen grosszelligen B-Zell Lymphom (DLBCL) treten in den ersten 5 Jahren auf. Die Standardbehandlung besteht in einer Salvage- und einer konsolidierenden Hochdosis-Chemotherapie mit klar kurativem Ziel. Die Prognose ist bei einem Frührezidiv bzw. refraktärer Situation, und vor allem wenn eine Hochdosis-Therapie nicht durchgeführt werden kann, wesentlich ungünstiger. Die Chimeric Antigen Receptor (CAR) T-Zell Therapie stellt für diese PatientInnen eine Behandlungsoption dar, die in den USA seit Oktober 2017, und am 22.10.2018 auch in der Schweiz zugelassen ist. Diese Therapie ist in jeder Hinsicht und für alle Beteiligten Neuland